Pyridinium salts and their use for the control of helicobacter bacteria

ABSTRACT

8-phenalkoxyimidazo 1,2-a!pyridinium salts are useful for controlling Helicobacter bacteria. Medicament compositions based on such compounds are prepared and used for the noted purpose.

This application is a 371 of PCT/EP94/01218 filed Apr. 20, 1994.

This application is a 371 of PCT/EP94/01218 filed Apr. 20, 1994.

FIELD OF APPLICATION OF THE INVENTION

The invention relates to novel pyridinium salts and their use for theproduction of medicaments which are to be employed for the treatment ofdiseases of the stomach and/or intestine, which are caused byHelicobacter bacteria.

1. Prior Art

A large number of European Patent Applications describe differentlysubstituted imidazo 1,2-a!pyridines (e.g. European Patent Applications 0033 094, 0 068 378, 0 120 589, 0 204 285, 0 228 006, 0 266 890, 0 268989 and 0 308 917) which are intended to be suitable for the preventionand treatment of ulcerative diseases of the stomach. It is common to theimidazo 1,2-a!pyridines disclosed in the European Patent Applicationsmentioned that they are not substituted in the 1-position.

2. Description of the Invention

It has now surprisingly been found that the pyridinium salts describedbelow, which in particular differ from the imidazo 1,2-a!pyridines ofthe prior art by the substituent in the 1-position, are active againstHelicobacter bacteria.

The invention thus relates to the compounds of the formula I (seeenclosed formula sheet), in which

R1 is C_(n) H_(2n) --A, where

A is hydrogen (H), 1-4C-alkylcarbonyl, carboxyl (COOH),1-4C-alkoxycarbonyl, carbamoyl (CONH₂), naphthyl, phenyl or phenyl whichis substituted by one or two identical or different substituents fromthe group consisting of halogen, 1-4C-alkyl, phenyl, 1-4C-alkoxy,-cyano,carboxyl (COOH), 1-4C-alkoxycarbonyl, trifluoromethyl andtrifluoromethoxy, and

n is the number 1, 2, 3 or 4,

R2 is 1-4C-alkyl,

R3 is hydrogen (H), 1-4C-alkyl, 2-4C-alkenyl, 2-4C-alkynyl,hydroxy-1-4C-alkyl, amino or cyanomethyl,

R4 is hydrogen (H), 1-4C-alkyl, 1-4C-alkoxy or halogen,

R5 is hydrogen (H), 1-4C-alkyl, 1-4C-alkoxy or halogen,

m is the number 1, 2 or 3 and

X.sup.θ is a suitable anion,

and the salts (betaines) of the carboxylic acids, where R1 is not methylif R2 is methyl, R3 is cyanomethyl, m is the number 1 and R4 and R5 arehydrogen (H).

Where A=hydrogen (H) and n=1, 2, 3 or 4, C_(n) H_(2n) --A is 1-4C-alkyl.

1-4C-alkyl is a straight-chain or branched alkyl radical having 1 to 4carbon atoms. Examples which may be mentioned are the butyl, isobutyl,sec-butyl, tert-butyl, propyl, isopropyl, ethyl and methyl radicals.

1-4C-alkylcarbonyl is a radical which, in addition to the carbonylgroup, contains one of the abovementioned 1-4C-alkyl radicals. Theacetyl radical is preferred.

1-4C-alkoxy is a radical which, in addition to the oxygen atom, containsone of the abovementioned 1-4C-alkyl radicals. The methoxy radical ispreferred.

1-4C-alkoxycarbonyl is a radical which, in addition to the carbonylgroup, contains one of the abovementioned 1-4C-alkoxy radicals. Themethoxycarbonyl and ethoxycarbonyl radicals are preferred.

Halogen within the meaning of the present invention is bromine, chlorineor fluorine.

2-4C-alkenyl is a straight-chain or branched alkenyl radical having 2 to4 carbon atoms. Examples which may be mentioned are the vinyl,2-butenyl, 3-butenyl and, in particular, the allyl radical.

2-4C-alkynyl is a straight-chain or branched alkynyl radical having 2 to4 carbon atoms. The propynyl radical may be mentioned as a preferredalkynyl radical.

Suitable anions X.sup.θ are in principle all anions, but particularlythose anions which are already present anyway in the alkylating agentsR1-X needed for the preparation of the compounds I, or those anionswhich are customarily used in active compounds in medicaments. Exampleswhich may be mentioned are the chloride, bromide, iodide andmethylsulfate ion.

Suitable salts of the carboxylic acids are those with suitable bases, azwitterion (betaine) being formed by the deprotonation. Examples ofbasic salts which may be mentioned are lithium, sodium, potassium,calcium, aluminum or magnesium salts, the corresponding bases beingemployed in the preparation of the salt--depending on whether they aremono- or polybasic bases and depending on which salt is desired--in anequimolar ratio or a quantitative ratio differing therefrom.

Compounds which may be emphasized are those of the formula I in which

R1 is C_(n) H_(2n) --A, where

A is hydrogen (H), naphthyl, phenyl or phenyl which is substituted byone or two identical or different substituents from the group consistingof halogen, 1-4C-alkyl, phenyl, 1-4C-alkoxy, cyano,1-4C-alkoxy-carbonyl, trifluoromethyl and trifluoromethoxy, and

n is the number 1, 2, 3 or 4,

R2 is 1-4C-alkyl,

R3 is 1-4C-alkyl, 3-4C-alkynyl, hydroxy-1-4C-alkyl or cyanomethyl

R4 is hydrogen (H),

R5 is hydrogen (H),

m is the number 1 or 2 and

X.sup.θ is a suitable anion,

where R1 is not methyl if R2 is methyl and R3 is cyanomethyl.

Compounds which may be particularly emphasized are those of the formulaI in which

R1 is C_(n) H_(2n) --A, where

A is phenyl or phenyl which is substituted by one or two identical ordifferent substituents from the group consisting of chlorine, fluorine,methyl, methoxy, cyano, methoxycarbonyl, trifluoromethyl andtrifluoromethoxy, and

n is the number 1 or 2,

R2 is methyl or ethyl

R3 is methyl, propynyl, hydroxymethyl or cyanomethyl,

R4 is hydrogen (H),

R5 is hydrogen (H),

m is the number 1 and

X.sup.θ is a suitable anion.

The invention further relates to a process for the preparation of thecompounds according to the invention and their salts. The processcomprises reacting compounds of the formula II (see enclosed formulasheet), in which R2, R3, R4, R5 and m have the meanings indicated above,with compounds of the formula III

    R1--X                                                      (III)

and, if desired, then converting compounds I obtained into their salts,or, if desired, then liberating the compounds I from salts of thecompounds I obtained.

The reaction of the compounds II with the compounds III is carried outin a manner familiar per se to the person skilled in the art insuitable, inert solvents. The following examples serve to illustrate theprocess according to the invention in greater detail. The abbreviation hstands for hour(s), RT for room temperature, and m.p. for melting point.The compounds and salts of these compounds mentioned in the examples area preferred subject of the invention.

EXAMPLES

1. 1-Benzyl-8-benzyloxy-2,3-dimethylimidazo 1,2-a!pyridinium bromide

A solution of 2 g of 8-benzyloxy-2,3-dimethylimidazo- 1,2-a!pyridine at50° C., dissolved in 40 ml of anhydrous acetone, is treated with 2.7 gof benzyl bromide and then heated under reflux for 16 h. The precipitateproduced in this process is filtered- off and washed with cold acetone.3.5 g of the title compound of m.p. 190°-192° C. are obtained.

2. 1-Benzyl-8-benzyloxy-3-cyanomethyl-2-methylimidazo- 1,2-a!pyridiniumbromide

The title compound of m.p. 188°-190° C. is obtained analogously toExample 1 by reaction of 8-benzyloxy-3-cyanomethyl-2-methylimidazo1,2,a!pyridine with benzyl bromide.

3. 8-Benzyloxy-1-(4-fluorobenzyl)-2,3-dimethylimidazo- 1,2-a!pyridiniumbromide

The title compound of m.p. 188°-191° C. is obtained by reaction of8-benzyloxy-2,3-dimethylimidazo 1,2-a!pyridine with 4-fluorobenzylbromide analogously to Example 1.

4. 8-Benzyloxy-1-(4-methoxycarbonylbenzyl)-2,3-dimethylimidazo1,2-a!pyridinium bromide

The title compound of melting range 177°-188° C. is obtained by reactionof 8-benzyloxy-2,3-dimethylimidazo 1,2-a!pyridine with methyl4-bromomethylbenzoate analogously to Example 1.

5. 8-Benzyloxy-2,3-dimethyl-1-phenethylimidazo 1,2-a!pyridinium bromide

The title compound of m.p. 173°-176° C. is obtained by reaction of8-benzyloxy-2,3-dimethylimidazo 1,2-a!pyridine with 2-phenethyl bromideanalogously to Example 1.

6. 8-Benzyloxy-3-cyanomethyl-2-methyl-1-phenethylimidazo1,2-a!pyridinium bromide

The title compound of m.p. 202°-205° C. is obtained by reaction of8-benzyloxy-3-cyanomethyl-2-methylimidazo 1,2-a!pyridine with2-phenethyl bromide analogously to Example 1.

7. 8-Benzyloxy-2-methyl-1-phenethyl-3- (2-propynyl)imidazo1,2-a!pyridinium bromide

The title compound of melting range 142°-150° C. is obtained by reactionof 8-benzyloxy-2-methyl-3-(2-propynyl)imidazo 1,2-a!pyridine with2-phenethyl bromide analogously to Example 1.

8. 1-Benzyl-8-benzyloxy-2-methyl-3-(2-propynyl)imidazo 1,2-a!pyridiniumbromide

The title compound of m.p. 190°-192° C. is obtained by reaction of8-benzyloxy-2-methyl-3-(2-propynyl)imidazo 1,2-a!pyridine with benzylbromide analogously to Example 1.

9. 8-Benzyloxy-2,3-dimethyl-1-(4-methylbenzyl)imidazo 1,2-a!pyridiniumbromide

The title compound of m.p. 212°-215° C. is obtained by reaction of8-benzyloxy-2,3-dimethylimidazo 1,2-a!pyridine with 4-methylbenzylbromide analogously to Example 1.

10. 8-Benzyloxy-1-(3,5-difluorobenzyl)-2,3-dimethylimidazo1,2-a!pyridinium bromide

The title compound of m.p. 195°-196° C. is obtained by reaction of8-benzyloxy-2,3-dimethylimidazo 1,2-a!pyridine with 3,5-difluorolbenzylbromide analogously to Example 1.

11. 8-Benzyloxy-1-(3-trifluoromethylbenzyl)-2,3-dimethylimidazo1,2-a!pyridinium bromide

The title compound of m.p. 187°-189° C. is obtained by reaction of8-benzyloxy-2,3-dimethylimidazo 1,2-a!pyridine with3-trifluoromethylbenzyl bromide analogously to Example 1.

12. 8-Benzyloxy-2,3-dimethyl-1-(2-naphthylmethyl)imidazo1,2-a!pyridinium bromide

The title compound of m.p. 195°-197° C. is obtained by reaction of8-benzyloxy-2,3-dimethylimidazo 1,2-a!pyridine with2-bromomethylnaphthalene analogously to Example 1.

13. 8-Benzyloxy-1-(3-cyanobenzyl)-2,3-dimethylimidazo 1,2-a!pyridiniumbromide

The title compound of m.p. 193°-195° C. is obtained by reaction of8-benzyloxy-2,3-dimethylimidazo 1,2-a!pyridine with3-bromomethylbenzonitrile analogously to Example 1.

14. 8-Benzyloxy-1-(4-chlorobenzyl)-2,3-dimethylimidazo 1,2-a!pyridiniumbromide

The title compound of m.p. 215°-217° C. is obtained by reaction of8-benzyloxy-2,3-dimethylimidazo 1,2-a!pyridine with 4-chlorobenzylbromide analogously to Example 1.

15. 8-Benzyloxy-1-(3,5-dimethylbenzyl)-2,3-dimethylimidazo1,2-a!pyridinium bromide

The title compound of m.p. 205°-207° C. is obtained by reaction of8-benzyloxy-2,3-dimethylimidazo 1,2-a!pyridine with 3,5-dimethylbenzylbromide analogously to Example 1.

16. 8-Benzyloxy-1-(3,4-dichlorobenzyl)-2,3-dimethylimidazo1,2-a!pyridinium bromide

The title compound of m.p. 199°-201° C. is obtained by reaction of8-benzyloxy-2,3-dimethylimidazo 1,2-a!pyridine with 3,4-dichlorobenzylbromide analogously to Example 1.

17. 8-Benzyloxy-1-(3,5-bis-(trifluoromethyl)benzyl)-2,3-dimethylimidazo1,2-a!pyridinium bromide

The title compound of m.p. 183°-186° C. is obtained by reaction of8-benzyloxy-2,3-dimethylimidazo 1,2-a!pyridine with3,5-bis-(trifluoromethyl)benzyl bromide analogously to Example 1.

18. 8-Benzyloxy-1-(4-biphenylmethyl)-2,3-dimethylimidazo1,2-a!pyridinium bromide

The title compound of m.p. 145°-150° C. is obtained by reaction of8-benzyloxy-2,3-dimethylimidazo 1,2-a!pyridine with4-bromomethylbiphenyl analogously to Example 1.

19. 8-Benzyloxy-3-cyanomethyl-1,2-dimethylimidazo 1,2-a!pyridiniumiodide

The title compound of m.p. 185°-186° C. is obtained by reaction of8-benzyloxy-3-cyanomethyl-2-methylimidazo 1,2-a!pyridine with methyliodide analogously to Example 1.

20. 8-Benzyloxy-1,2,3-trimethylimidazo 1,2-a!pyridinium iodide

The title compound of m.p. 218°-219° C. is obtained by reaction of8-benzyloxy-2,3-dimethylimidazo 1,2-a!pyridine with methyl iodideanalogously to Example 1.

21. 8-Benzyloxy-3-cyanomethyl-1,2-dimethylimidazo 1,2-a!pyridiniummethosulfate

A solution of 100 mg of 8-benzyloxy-3-cyanomethyl-2-methylimidazo1,2-a!pyridine in 3 ml of dry acetone is treated with 45 mg of dimethylsulfate and stirred at RT for 16 h. The precipitate formed in thisprocess is filtered off, washed with a little diethyl ether and dried.90 mg of the title compound of m.p. 185°-187° C. are obtained.

22. 8-Benzyloxy-1-(4-trifluoromethylbenzyl)-2,3-dimethylimidazo1,2-a!pyridinium bromide

The title compound of m.p. 207°-209° C. is obtained by reaction of8-benzyloxy-2,3-dimethylimidazo 1,2-a!pyridine with4-trifluoromethylbenzyl bromide analogously to Example 1.

23. 8-Benzyloxy-1-(3,4-difluorobenzyl)-2,3-dimethylimidazo1,2-a!pyridinium bromide

The title compound of m.p. 191°-193° C. is obtained by reaction of8-benzyloxy-2,3-dimethylimidazo 1,2-a!pyridine with 3,4-difluorolbenzylbromide analogously to Example 1.

24. 8-Benzyloxy-1-(3-chlorobenzyl)-2,3-dimethylimidazo 1,2-a!pyridiniumbromide

The title compound of m.p. 183°-185° C. is obtained analogously toExample 23 by reaction with 3-chlorobenzyl bromide.

25. 8-Benzyloxy-1-(4-trifluoromethoxybenzyl)-2,3-dimethylimidazo1,2-a!pyridinium bromide

The title compound of m.p. 148°-151° C. is obtained analogously toExample 23 by reaction with 4-trifluoromethoxybenzyl bromide.

26. 8-Benzyloxy-1-(3-trifluoromethoxybenzyl)-2,3-dimethylimidazo1,2-a!pyridinium bromide

The title compound of m.p. 137°-140° C. is obtained analogously toExample 23 by reaction with 3-trifluoromethoxybenzyl bromide.

27. 8-Benzyloxy-1-(3-methylbenzyl)-2,3-dimethylimidazo 1,2-a!pyridiniumbromide

The title compound of m.p. 180°-182° C. is obtained analogously toExample 23 by reaction with 3-methylbenzyl bromide.

28. 8-Benzyloxy-1-(4-t-butylbenzyl)-2,3-dimethylimidazo 1,2-a!pyridiniumbromide

The title compound of m.p. 200°-202° C. is obtained analogously toExample 23 by reaction with 4-t-butylbenzyl bromide.

29. 8-Benzyloxy-2-methyl-1-(3,5-dimethylbenzyl)-3-(2-propynyl)imidazo1,2-a!pyridinium bromide

The title compound of m.p. 200°-202° C. is obtained by reaction of8-benzyloxy-2-methyl-3-(2-propynyl)imidazo 1,2-a!pyridine with3,5-dimethylbenzyl bromide analogously to Example 1.

30. 8-Benzyloxy-1-(4-cyanobenzyl)-2,3-dimethylimidazo 1,2-a!-pyridiniumbromide

The title compound of m.p. 143°-147° C. is obtained by reaction with4-cyanobenzyl bromide analogously to Example 23.

31. 8-Benzyloxy-2,3-dimethyl-1-(2,4-dimethylbenzyl)imidazo1,2-a!-pyridinium chloride

The title compound of m.p. 192°-195° C. is obtained analogously toExample 23 by reaction with 2,4-dimethylbenzyl chloride.

32. 8-Benzyloxy-2,3-dimethyl-1-(2,5-dimethylbenzyl)imidazo1,2-a!pyridinium chloride

The title compound of m.p. 197°-200° C. is obtained analogously toExample 23 by reaction with 2,5-dimethylbenzyl chloride.

33. 8-Benzyloxy-2,3-dimethyl-1-(3,5-dimethylbenzyl)imidazo1,2-a!pyridinium chloride

The title compound of m.p. 168°-173° C. is obtained analogously toExample 23 by reaction with 3,5-dimethylbenzyl chloride.

34. 8-Benzyloxy-1-ethyl-2,3-dimethylimidazo 1,2-a!pyridinium bromide

The title compound of m.p. 193°-195° C. is obtained analogously toExample 23 by reaction with ethyl bromide.

35. 8-Benzyloxy-1-n-propyl-2,3-dimethylimidazo 1,2-a!pyridinium bromide

The title compound of m.p. 206°-209° C. is obtained analogously toExample 23 by reaction with 1-bromopropane.

36. 8-Benzyloxy-1-n-butyl-2,3-dimethylimidazo 1,2-a!pyridinium bromide

The title compound of m.p. 172°-174° C. is obtained analogously toExample 23 by reaction with 1-bromobutane.

37. 2,3-Dimethyl-1-(3,5-dimethylbenzyl)-8-(2-phenethoxy)imidazo1,2-a!pyridinium bromide

The title compound of m.p. 198°-200° C. is obtained analogously toExample 1 by reaction of 2,3-dimethyl-8-(2-phenethoxy)imidazo1,2-a!pyridine with3,5-dimethylbenzyl bromide.

38. 8-Benzyloxy-1-(3,5-dimethylbenzyl)-2-methylimidazo 1,2-a!pyridiniumbromide

The title compound of m.p. 195°-197° C. is obtained analogously toExample 23 by reaction with 3,5-dimethylbenzyl bromide.

39. 8-Benzyloxy-2-ethyl-3-methyl-1-(3,5-dimethylbenzyl)imidazo1,2-a!pyridinium bromide

The title compound of m.p. 214°-216° C. is obtained analogously toExample 1 by reaction of 8-benzyloxy-2-ethyl-3-methylimidazo1,2-a!pyridine with 3,5-dimethylbenzyl bromide.

40. 8-Benzyloxy-2-ethyl-3-hydroxymethyl-1-(3,5-dimethylbenzyl)imidazo1,2-a!-pyridinium bromide

The title compound of m.p. 208°-210° C. is obtained analogously toExample 1 by reaction of 8-benzyloxy-2-ethyl-3-hydroxymethylimidazo1,2-a!pyridine with 3,5-dimethylbenzyl bromide.

41. 8-Benzyloxy-1-(3-methoxycarbonylbenzyl)-2,3-dimethylimidazo1,2-a!pyridinium bromide

The title compound of m.p. 150°-154° C. is obtained analogously toExample 23 by reaction with 3-methoxycarbonylbenzyl bromide.

42. 8-Benzyloxy-1-(3-methoxybenzyl)-2,3-dimethylimidazo 1,2-a!pyridiniumchloride

The title compound of m.p. 144°-148° C. is obtained analogously toExample 23 by reaction with 3-methoxybenzyl chloride.

43. 8-Benzyloxy-1-(3,4-dimethylbenzyl)-2,3-dimethylimidazo1,2-a!pyridinium chloride

The title compound of m.p. 196°-201° C. is obtained analogously toExample 23 by reaction with 3,4-dimethylbenzyl chloride.

Industrial Utility

The compounds of the formula I in which R1, A, n, R2, R3, R4, R5, m andX.sup.θ have the meaning indicated above, and their salts, have usefulpharmacological properties which make them industrially utilizable. Inparticular, they have an antiulcerogenic activity and a marked activityagainst Helicobacter bacteria. Moreover, the compounds according to theinvention are distinguished by a high selectivity of action,. the lackof significant side effects and a large therapeutic breadth.

The excellent activity of compounds of the formula I and their saltsagainst Helicobacter bacteria makes possible their use in human medicineas active compounds for the treatment of ulcerative diseases and ofillnesses which are based on Helicobacter bacteria.

The invention therefore further relates to a method for the treatment ofmammals, in particular humans, suffering from ulcerative diseases andfrom illnesses which are based on Helicobacter bacteria. The methodcomprises administering to the ill individual a therapeutically activeand pharmacologically tolerable amount of one or more compounds of theformula I and/or their pharmacologically tolerable salts.

The invention additionally relates to the compounds of the formula I andtheir pharmacologically tolerable salts for administration in thetreatment of ulcerative diseases and of illnesses which are based onHelicobacter bacteria.

The invention also comprises the use of compounds of the formula I andtheir pharmacologically tolerable salts in the preparation ofmedicaments which are employed for the control of ulcerative diseasesand those illnesses which are based on Helicobacter bacteria.

The invention further relates to medicaments for the treatment ofulcerative diseases and for the control of Helicobacter bacteria, whichcomprise one or more compounds of the general formula I and/or theirpharmacologically tolerable salts.

Of the Helicobacter strains against which the compounds of the formula Iprove to be active, the strain Helicobacter pylori may be mentioned inparticular.

The medicaments are prepared by processes known per se which arefamiliar to the person skilled in the art. The medicaments employed arethe pharmacologically active compounds of the formula I and their salts(=active compounds), either as such, or preferably in combination withsuitable pharmaceutical auxiliaries, e.g. in the form of tablets, coatedtablets, capsules, emulsions, suspensions, gels or solutions, the activecompound content advantageously being between 0.1 and 95%.

The person skilled in the art is familiar with the auxiliaries which aresuitable for the desired pharmaceutical formulations on the basis of hisexpert knowledge. In addition to solvents, gel formers, tabletauxiliaries and other active compound excipients, for exampleantioxidants, dispersants, emulsifiers, antifoams, flavor corrigents,preservatives, solubilizers, colorants or permeation promoters andcomplexing agents (e.g. cyclodextrins) can be used.

The active compounds can be administered, for example, parenterally(e.g. intravenously) or, in particular, orally.

In general, in human medicine the active compounds are administered in adaily dose of approximately 0.5 to 50, preferably 1 to 30, mg/kg of bodyweight, if appropriate in the form of several, preferably 2 to 6,individual doses to achieve the desired result.

Biological Investigations

The compounds according to the invention were investigated with respectto their activity against Helicobacter pylori following the methodologydescribed by Tomoyuki Iwahi et al. (Antimicrobial Agents andChemotherapy, 1991, 490-496) using Columbia agar (Oxoid) and with agrowth period of 4 days. For the compounds investigated, the MIC valuesshown in the table below resulted in this case (the numbers of thecompounds indicated correspond to the numbers of the examples).

    ______________________________________                                        Compound      MIC Value                                                       No.           (μg/ml)                                                      ______________________________________                                        3             ≦10                                                      4             ≦10                                                      5             ≦10                                                      6             ≦10                                                      7             ≦10                                                      10            ≦10                                                      12            ≦10                                                      13            ≦10                                                      18            ≦10                                                      ______________________________________                                    

I claim:
 1. A compound of the formula I ##STR1## in which R1 is C_(n)H_(2n) --A, whereA is hydrogen (H), 1-4C-alkylcarbonyl, carboxyl (COOH),1-4C-alkoxycarbonyl, carbamoyl (CONH₂), naphthyl, phenyl or phenyl whichis substituted by one or two identical or different substituents fromthe group consisting of halogen, 1-4C-alkyl, phenyl, 1-4C-alkoxy, cyano,carboxyl (COOH), 1-4C-alkoxycarbonyl, trifluoromethyl andtrifluoromethoxy, and n is the number 1, 2, 3 or 4, R2 is 1-4C-alkyl, R3is hydrogen (H), 1-4C-alkyl, 2-4C-alkenyl, 2-4C-alkynyl,hydroxy-1-4C-alkyl, amino or cyanomethyl, R4 is hydrogen (H),1-4C-alkyl, 1-4C-alkoxy or halogen, R5 is hydrogen (H), 1-4C-alkyl,1-4C-alkoxy or halogen, m is the number 1, 2 or 3 and X.sup.θ is asuitable anion, and the a salt (betaine) of a carboxylic acid thereof,where R1 is not methyl when R2 is methyl, R3 is cyanomethyl, m is thenumber 1 and R4 and R5 are hydrogen (H).
 2. A compound of formula I asclaimed in claim 1, in whichR1 is C_(n) H_(2n) --A, where A is hydrogen(H), naphthyl, phenyl or phenyl which is substituted by one or twoidentical or different substituents from the group consisting ofhalogen, 1-4C-alkyl, phenyl, 1-4C-alkoxycarbonyl and trifluoromethyl andn is the number 1 or 2, R2 is 1-4C-alkyl, R3 is 1-4C-alkyl, 3-4C-alkynylor cyanomethyl, R4 is hydrogen (H), R5 is hydrogen (H), m is the number1 and X.sup.θ is a suitable anion, where R1 is not methyl when R2 ismethyl and R3 is cyanomethyl.
 3. A compound of formula I as claimed inclaim 1, in whichR1 is C_(n) H_(2n) --A, where A is hydrogen (H),naphthyl, phenyl or phenyl which is substituted by one or two identicalor different substituents from the group consisting of halogen,1-4C-alkyl, phenyl, 1-4C-alkoxy, cyano, 1-4C-alkoxycarbonyl,trifluoromethyl and trifluoromethoxy, and n is the number 1, 2, 3 or 4,R2 is 1-4C-alkyl, R3 is 1-4C-alkyl, 3-4C-alkynyl, hydroxy-1-4C-alkyl orcyanomethyl R4 is hydrogen (H), R5 is hydrogen (H), m is the number 1 or2 and X.sup.θ is a suitable anion, where R1 is not methyl when R2 ismethyl and R3 is cyanomethyl.
 4. A compound of formula I as claimed inclaim 1, in whichR1 is C_(n) H_(2n) --A, where A is phenyl or phenylwhich is substituted by one or two identical or different substituentsfrom the group consisting of chlorine, fluorine, methyl, methoxy, cyano,methoxycarbonyl, trifluoromethyl and trifluoromethoxy, and n is thenumber 1 or 2, R2 is methyl or ethyl R3 is methyl, propynyl,hydroxymethyl or cyanomethyl, R4 is hydrogen (H), R5 is hydrogen (H), mis the number 1 and X.sup.θ is a suitable anion.
 5. A process for thepreparation of a compound of formula I as claimed in claim 1, or a saltthereof, which comprises reacting a compound of formula II ##STR2## inwhich R2, R3, R4, R5 and m have the meanings indicated in claim 1, witha compound of formula III

    R1--X                                                      (III)

in which R1 has the meaning indicated in claim 1 and X is the covalentlybonded form of the suitable anion X.sup.θ, and, if desired, thenconverting the compound I obtained into a salt, or, if desired, thenliberating the the compound I from a salt of the compound I obtained. 6.A medicament composition comprising a suitable carrier and, as activecomponent, an effective amount of a compound of claim 1 or apharmacologically-tolerable salt thereof.
 7. A method of treating amammal afflicted with an illness caused by Helicobacter bacteria andwhich comprises administering to such mammal an effective amount of acompound of formula I ##STR3## in which R1 is C_(n) H_(2n) A, whereA ishydrogen (H), 1-4C-alkylcarbonyl, carboxyl (COOH), 1-4C-alkoxycarbonyl,carbamoyl (CONH₂), naphthyl, phenyl or phenyl which is substituted byone or two identical or different substitutents selected from the groupconsisting of halogen, 1-4C-alkyl, phenyl, 1-4C-alkoxy, cyano, carboxyl(COOH), 1-4C-alkoxycarbonyl, trifluoromethyl and trifluoromethoxy, n isthe number 1, 2, 3, or 4, R2 is 1-4C-alkyl, R3 is hydrogen (H),1-4c-alkyl, 2-4C-alkenyl, 2-4C-alkynyl, hydroxy-1-4C-alkyl, amino orcyanomethyl, R4 is hydrogen (h), 1-4C-alkyl, 1-4C-alkoxy or halogen, R5is hydrogen (H), 1-4C-alkyl, 1-4C-alkoxy or halogen, m is the number 1,2 or 3 and X.sup.θ is a suitable anion, or a pharmacologically-tolerablesalt (betaine) of a carboxylic acid thereof.
 8. In compounding amedicament composition having an effective amount of an active componentfor controlling Helicobacter bacteria, the improvement wherein theactive component is a compound of claim 1 or apharmacologically-tolerable salt (betaine) of a carboxylic acid thereof.9. A method of claim 7 wherein the Helicobacter bacteria areHelicobacter pylori.
 10. A method of claim 8 wherein the Helicobacterbacteria are Helicobacter pylori.
 11. A method of treating a mammalafflicted with an illness caused by Helicobacter bacteria, whichcomprises administering to the mammal an effective amount of apharmacologically-acceptable compound of claim 1.